The compound 4-(6'-methoxy-2'-naphthyl)-3-buten-2-one is a valuable intermediate in the manufacture of the nonsteroidal anti-inflammatory known as nabumetone. The compound and prior art methods of its manufacture have been described in U.S. Pat. Nos. 4,061,779; 4,221,741; and 4,420,639 assigned to the Beecham Group Limited.
These prior art processes involve (i) the synthesis of 6-methoxy-2-naphthaldehyde by a Grignard reaction of 2-bromo-6-methoxynaphthalene with N,N-dimethylformamide; the base catalyzed aldol condensation of the aldehyde with acetone to form 4-(6'-methoxy-2'-naphthyl)-3-buten-2-one and the subsequent catalytic hydrogenation of that compound using 10% palladium on carbon; or, (ii) the condensation of 6'-methoxy-2'-acetonaphthone with ethyl acetate using sodium hydride in dimethyl sulfoxide and the subsequent hydrogenation of that compound with 10% palladium on carbon as in (i) above.
R. F. Heck, in Pure and Applied Chemistry, Vol. 50, pp. 691-701, (1978), has described a new vinylic substitution reaction. ##STR1##
According to the Heck article, the reaction occurs in the presence of a "palladium" catalyst. Such catalyst comprises, usually, a complex of a palladium (II) salt and a phosphine ligand. Heck has shown the reaction of aromatic bromides with various unsaturated alcohols and esters. He states, however, that .alpha., .beta.-unsaturated ketones and aldehydes are polymerized under the reaction conditions.
Others have more recently studied the vinylic substitution reaction. Among these are A. J. Chalk and S. A. Magennis in Journal of Organic Chemistry, Vol. 41, pp. 273-278 and 1206-1209 (1976); and J. B. Melpolder and Heck, Journal of Organic Chemistry, Vol. 41, pp. 265-272 (1976). S. Cacchi and G. Palmieri in Synthesis, July, 1984, pp. 575-577, report the palladium catalyzed synthesis of a disubstituted .alpha., .beta.-unsaturated carbonyl compounds with aryl iodides. S. Cacchi and A. Arcadi have written extensively on the reaction in an article in Journal of Organic Chemistry, Vol. 48, pp. 4236-4240 (1983).